Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway
Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway
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DOI：
10.1007/s10571-008-9286-x
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发表时间：
2008-12-01
影响因子：
4
通讯作者：
So, Kwok-Fai
中科院分区：
文献类型：
--
作者：
Li, Suk-Yee;Yau, Suk-Yu;So, Kwok-Fai
在本研究中，我们研究了影响表达黑视素的视网膜神经节细胞（mRGCs）抗损伤特性的因素。由于磷脂酰肌醇-3激酶（PI 3 K）/Akt信号通路是已知的神经元细胞存活的通路之一，我们通过应用PI 3 K/Akt特异性抑制剂来研究损伤后mRGCs的存活。采用Sprague-Dawley大鼠建立单侧视神经切断和高眼压两种损伤模型。损伤后玻璃体内注射PI 3 K/Akt抑制剂以抑制PI 3 K/Akt信号通路。在指定的存活时间后解剖视网膜，使用黑视素抗体进行免疫组织化学以使mRGCs可视化并计数mRGCs的数量。还检查了黑视蛋白和磷酸化Akt（pAkt）的共表达。与不表达黑视素的RGCs的存活相比，mRGCs显示出对损伤的显著抗性并共表达pAkt。PI 3 K/Akt抑制剂的应用降低了损伤后mRGCs的存活率。我们以前的研究表明，mRGC对诱导高眼压后的损伤不太敏感。在这项研究中，我们报告说，mRGCs的损伤抵抗更严重类型的损伤，视神经横断。更重要的是，发现PI 3 K/Akt通路在维持损伤后mRGCs的存活中起作用。
In the present study, we studied the factors that contribute to the injury-resistant property of melanopsin-expressing retinal ganglion cells (mRGCs). Since phosphatidylinositol-3 kinase (PI3 K)/Akt signaling pathway is one of the well-known pathways for neuronal cell survival, we investigated the survival of mRGCs by applying the PI3 K/Akt specific inhibitors after injury. Two injury models, unilateral optic nerve transection and ocular hypertension, were adopted using Sprague-Dawley rats. Inhibitors of PI3 K/Akt were injected intravitreally following injuries to inhibit the PI3 K/Akt signaling pathway. Retinas were dissected after designated survival time, immunohistochemistry was carried out to visualize the mRGCs using melanopsin antibody and the number of mRGCs was counted. Co-expression of melanopsin and phospho-Akt (pAkt) was also examined. Compared to the survival of non-melanopsin-expressing RGCs, mRGCs showed a marked resistance to injury and co-expressed pAkt. Application of PI3 K/Akt inhibitors decreased the survival of mRGCs after injury. Our previous study has shown that mRGC are less susceptible to injury following the induction of ocular hypertension. In this study, we report that mRGCs were injury-resistant to a more severe type of injury, the optic nerve transection. More importantly, the PI3 K/Akt pathway was found to play a role in maintaining the survival of mRGCs after injury.